Prevalence of Admission Hyponatremia in Patients With Diabetes Treated With and Without an SGLT2 inhibitor

Abstract

BACKGROUND Hyponatremia often reflects a free water excess. Sodium/glucose co-transporter 2 (SGLT2) inhibitors increase free water excretion through glucose-induced osmotic diuresis. In two randomized double-blind placebo-controlled trials in patients with a syndrome of inappropriate antidiuresis (SIAD), we showed that empagliflozin increased plasma sodium concentration more effectively than placebo. We hypothesized that long-term therapy with SGLT2 inhibitors might reduce the prevalence of hyponatremia on hospital admission. METHOD In this retrospective analysis, we extracted data from adult patients with type 2 diabetes (T2DM), hospitalized at the University Hospital Basel between 2015 and 2020. Patients with an SGLT2 inhibitor on admission were matched 1:1 according to age, gender, diagnosis of heart failure and principal diagnosis, to patients without an SGLT2 inhibitor on admission. The primary outcome was the prevalence of hyponatremia (plasma sodium concentration corrected for glycemia <135 mmol/L) on admission. RESULTS We analyzed 821 diabetic patients treated with and 821 diabetic patients without an SGLT2 inhibitor on admission. Hyponatremia prevalence on admission was 9.9% in the treated group, and 8.9% in the matched control group (p = 0.554), i.e., the risk for hyponatremia did not differ (multivariable adjusted OR = 1.08, 95%-CI: 0.72-1.44, p = 0.666). There was no difference in the median [IQR] plasma sodium concentration between both groups (treated: 140 mmol/L [138-142], controls: 140 mmol/L [138-142]; p = 0.1017). CONCLUSION Based on these retrospective findings, treatment with SGLT2 inhibitors does not prevent hyponatremia. However, prospective randomized data suggest their efficacy at a higher dosage in overt SIAD.